Overlap of Endocrine Hormone Expression in the Mouse Intestine Revealed by Transcriptional Profiling and Flow Cytometry
Overlap of Endocrine Hormone Expression in the Mouse Intestine Revealed by Transcriptional Profiling and Flow Cytometry
复制标题
DOI：
10.1210/en.2011-2170
复制
发表时间：
2012-07-01
期刊：
影响因子：
4.8
通讯作者：
Gribble, Fiona M.
中科院分区：
文献类型：
--
作者：
Habib, Abdella M.;Richards, Paul;Gribble, Fiona M.
肠道分泌一系列激素，具有重要的局部和远端作用，包括控制胰岛素分泌和食欲。已经描述了许多肠内分泌细胞类型，每种类型的特征在于不同的激素特征，例如产生葡萄糖依赖性促胰岛素多肽（GIP）的K细胞、产生胰高血糖素样肽-1（GLP-1）的L细胞和产生胆囊收缩素（CCK）的I细胞。为了评价L-、K-和其他肠内分泌细胞之间的相似性，通过流式细胞术和基于微阵列的转录组学纯化并分析原代鼠L-和K-细胞以及胰腺α-和β-细胞。通过微阵列表达谱分析，来自上小肠（SI）的L细胞比结肠L细胞更接近上SI K细胞。上SIL-细胞群体表达的信息激素经典定位于不同的肠内分泌细胞类型，包括GIP，CCK，分泌素，和神经降压素。通过免疫染色和荧光激活细胞分选分析，大多数结肠L细胞含有GLP-1和PeptideYY。在上SI中，大多数L细胞含有CCK，约10%为GIP阳性，约20%为PeptideYY阳性。上SIK细胞与GLP-1约有10%重叠，与生长抑素约有6%重叠。肠内分泌特异性转录因子的微阵列，其中很少有不同的肠内分泌细胞群。通过定量RT-PCR，Etv 1、Prox 1和Pax 4在L细胞中相对于K细胞显著富集。总之，我们的数据表明上SIL-、K-和I-细胞之间存在很强的重叠，并表明它们可能包含单一细胞类型，其中单个细胞表现出激素谱，这可能反映了诸如沿肠沿着的位置和暴露于膳食营养素的因素。（内分泌学153：3054-3065，2012）
The intestine secretes a range of hormones with important local and distant actions, including the control of insulin secretion and appetite. A number of enteroendocrine cell types have been described, each characterized by a distinct hormonal signature, such as K-cells producing glucose-dependent insulinotropic polypeptide (GIP), L-cells producing glucagon-like peptide-1 (GLP-1), and I-cells producing cholecystokinin (CCK). To evaluate similarities between L-, K-, and other enteroendocrine cells, primary murine L-and K-cells, and pancreatic alpha- and beta-cells, were purified and analyzed by flow cytometry and microarray-based transcriptomics. By microarray expression profiling, L cells from the upper small intestinal (SI) moreclosely resembled upper SI K-cells than colonic L-cells. Upper SI L-cell populations expressed message for hormones classically localized to different enteroendocrine cell types, including GIP, CCK, secretin, and neurotensin. By immunostaining and fluorescence-activated cell sorting analysis, most colonic L-cells contained GLP-1 and PeptideYY In the upper SI, most L-cells contained CCK, approximately 10% were GIP positive, and about 20% were PeptideYY positive. Upper SI K-cells exhibited approximately 10% overlap with GLP-1 and 6% overlap with somatostatin. Enteroendocrine-specific transcription factors were identified from the microarrays, of which very few differed between the enteroendocrine cell populations. Etv1, Prox1, and Pax4 were significantly enriched in L-cells vs. K cells by quantitative RT-PCR. In summary, our data indicate a strong overlap between upper SI L-, K-, and I-cells and suggest they may rather comprise a single cell type, within which individual cells exhibit a hormonal spectrum that may reflect factors such as location along the intestine and exposure to dietary nutrients. (Endocrinology 153: 3054-3065, 2012)